Inhibited Tumor Cell Migration Research Articles

In vitro wound healing: Inhibition activity of insect‐derived mAb CO17‐1A in human colorectal cancer cell migration

AbstractThe monoclonal antibody (mAb) CO17‐1A specifically binds to the tumor‐associated cell surface glycoprotein GA733 in colorectal cancer cells. Thus, mAb CO17‐1A has the potential to act as an immune therapeutic protein against colorectal cancer. Recently, it was shown that the baculovirus insect cell expression system produces anti‐colorectal cancer mAb CO17‐1A. In this study, the colorectal cancer antibody mAb CO17‐1A fused to the endoplasmic reticulum (ER) retention signal sequence (KDEL), and the (mAb CO17‐1AK) was expressed in Spodoptera frugiperda Sf9 insect cells. The yield, cell cytotoxicity, and in vitro anti‐tumor activity of mAb CO17‐1AK were verified. Western blotting was performed to confirm that both heavy and light chains of mAb CO17‐1A were expressed in Sf9 insect cells. The insect‐derived mAb (mAbI) CO17‐1A was purified using a protein G affinity column. An in vitro wound healing assay was conducted to determine the inhibition activity of mAb CO17‐1A during tumor cell migration, showing that mAbI CO17‐1AK was effective as mammalian‐derived mAb CO17‐1A (mAbM CO17‐1A). These results suggest that the insect cell expression system can produce and properly assemble mAbs that inhibit tumor cell migration.

Local Delivery of Gemcitabine Inhibits Pancreatic and Cholangiocarcinoma Tumor Growth by Promoting Epidermal Growth Factor Receptor Degradation.

Gemcitabine is clinically used to treat certain types of cancers, including pancreatic and biliary cancer. We investigated the signal transduction pathways underlying the local antitumor effects of gemcitabine-eluting membranes (GEMs) implanted in pancreatic/biliary tumor-bearing nude mice. Here, we report that GEMs increased the E3 ubiquitin ligase c-CBL protein level, leading to degradation of epidermal growth factor receptor (EGFR) in SCK and PANC-1 cells. GEMs decreased the RAS and PI3K protein levels, leading to a reduction in the protein levels of active forms of downstream signaling molecules, including PDK, AKT, and GSK3β. GEM reduced proliferation of cancer cells by upregulating cell cycle arrest proteins, particularly p53 and p21, and downregulating cyclin D1 and cyclin B. Moreover, GEMs reduced the levels of proangiogenic factors, including VEGF, VEGFR2, CD31, and HIF-1α, and inhibited tumor cell migration and invasion by inducing the expression of E-cadherin and reducing that of N-cadherin, snail, and vimentin. We demonstrated that local delivery of gemcitabine using GEM implants inhibited tumor cell growth by promoting c-CBL-mediated degradation of EGFR and inhibiting the proliferation, angiogenesis, and epithelial–mesenchymal transition of pancreatic/biliary tumors. Use of gemcitabine-eluting stents can improve stent patency by inhibiting the ingrowth of malignant biliary obstructions.

LincRNA-p21 knockdown reversed tumor-associated macrophages function by promoting MDM2 to antagonize* p53 activation and alleviate breast cancer development.

Tumor-associated macrophages (TAMs) are important regulators of the complex interplay between immune system and breast cancer. TAMs fuel the cancer progression and metastasis by reprogramming their specific functional phenotype in cancer settings. Therefore, it is important to clarify the mechanisms of shaping specific functional phenotype of macrophages in tumor milieu. LncRNA profiles of TAMs were identified by LncRNA microarray. Flow cytometry was used to detect the surface markers of TAMs. The co-localization among lincRNA-p21, p53 and Mouse Double Minute 2 (MDM2) was identified by FISH probe and immunofluorescence. PyVT-MMTV and BALB/c mice were used for in vivo analysis. In the present work, we found that lincRNA-p21 significantly up-regulated in 4T1 educated macrophages. LincRNA-p21 knockdown facilitated macrophage polarization into pro-inflammatory M1 in tumor microenvironment, which might be caused by MDM2 eliciting proteasome-dependent degradation to p53 and activated NF-κB and STAT3 pathway. TAMs with lincRNA-p21 knockdown induced cancer cell apoptosis, inhibited tumor cell migration and invasion. In vivo, lincRNA-p21 knockdown macrophage adoptive transfer could alleviate breast cancer progression. Our results indicated that lincRNA-p21 was a key regulator of TAMs function in tumor milieu. Our data also shed a light on novel therapeutic targets of tumors characterized by monocytes/macrophages infiltration.

A novel role of tumor suppressor ZMYND8 in inducing differentiation of breast cancer cells through its dual-histone binding function

Accumulating evidences indicate the involvement of epigenetic deregulations in cancer. While some epigenetic regulators with aberrant functions in cancer are targeted for improving therapeutic outcome in patients, reinstating the functions of tumor-suppressor-like epigenetic regulators might further potentiate anti-cancer therapies. Epigenetic reader zinc-finger MYND-type-containing 8 (ZMYND8) has been found to be endowed with multiple anti-cancer functions like inhibition of tumor cell migration and proliferation. Here, we report another novel tumor suppressor role of ZMYND8 as an inducer of differentiation in breast cancer cells, by upregulating differentiation genes. Interestingly, we also demonstrated that ZMYND8 mediates all its antitumor roles through a common dual-histone mark binding to H4K16Ac and H3K36Me2. We validated these findings by both biochemical and biophysical analyses. Furthermore, we also confirmed the differentiationinducing potential of ZMYND8 in vivo, using 4T1 murine breast cancer model in Balb/c mice. Differentiation therapy holds great promise in cancer therapy, since it is non-toxic and makes the cancer cells therapysensitive. In this scenario, we propose epigenetic reader ZMYND8 as a potential therapeutic candidate for differentiation therapy in breast cancer.

Immunomodulatory Activities of the Heparan Sulfate Mimetic PG545.

Heparanase regulates multiple biological activities that enhance tumor growth and metastatic spread. Heparanase cleaves and degrades heparan sulfate (HS), a key structural component of the extracellular matrix that serves as a barrier to cell invasion and also as a reservoir for cytokines and growth factors critical for tumor growth and metastasis. For this reason, heparanase is an attractive target for the development of novel anti-cancer therapies. Pixatimod (PG545), a heparanase inhibitor, has shown promising results in the treatment of multiple tumor types. PG545 offers a diversity of mechanisms of action in tumor therapy that include angiogenic inhibition, inhibition of growth factor release, inhibition of tumor cell migration, tumorcell apoptosis, activation of ER stress response, dysregulation of autophagy, and NK cell activation. Further investigation into the role that heparanase and its inhibitors play in tumor therapy can lead to the development of effective tumor therapies.

Calumenin-1 Interacts with Climp63 to Cooperatively Determine the Luminal Width and Distribution of Endoplasmic Reticulum Sheets.

SummaryThe ER is composed of distinct structures like tubules, matrices, and sheets, all of which are important for its various functions. However, how these distinct ER structures, especially the perinuclear ER sheets, are formed remains unclear. We report here that the ER membrane protein Climp63 and the ER luminal protein calumenin-1 (Calu1) collaboratively maintain ER sheet morphology. We show that the luminal length of Climp63 is positively correlated with the luminal width of ER sheets. Moreover, the lumen-only mutant of Climp63 dominant-negatively narrows the lumen of ER sheets, demonstrating that Climp63 acts as an ER luminal bridge. We also reveal that Calu1 specifically interacts with Climp63 and antagonizes Climp63 in terms of both ER sheet distribution and luminal width. Together, our data provide insight into how the structure of ER sheets is maintained and regulated.

LHX3 is an advanced-stage prognostic biomarker and metastatic oncogene in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common cancer and exhibits high morbidity and mortality in the world. We recently identified LHX3 as a preferentially expressed gene with a possible involvement in HCC. To determine the expression, clinical relevance, prognostic significance and functions of LHX3 in HCC. LHX3 expression was assessed in 190 cancerous and 40 adjacent non-cancerous tissues by PCR, western blot and immunohistochemistry. Associations between LHX3 expression and clinicopathological characteristics of patients were investigated. Correlations between LHX3 expression and overall survival of patients were analyzed by Kaplan-Meier and Cox-regression methods. Functional roles of LHX3 were evaluated by transwell assays. LHX3 expression is significantly increased in carcinoma tissues, and associated with clinical stage and metastasis of patients. LHX3 expression is much higher in the advanced-stage patients than the early-stage patients, and is sharply increased in metastasic patients. High LHX3 expression is associated with unfavorable overall survival, and is an independent prognostic factor of patients. Moreover, LHX3 is an unfavorable and independent prognostic factor unique to advanced-stage patients. Knockdown expression of LHX3 obviously inhibits tumor cell migration and invasion. LHX3 is an advanced-stage prognostic biomarker, and acts as a new potential metastatic oncogene in HCC.

Evidence and impact of neutrophil extracellular traps in malignant melanoma.

Ulceration of melanoma is associated with neutrophil infiltrates and lower survival rates opposite to non-ulcerated melanoma. Neutrophils release neutrophil extracellular traps (NETs) that are chromatin structures loaded with antimicrobial proteins. Since NETs have been correlated with tumor progression, we investigated whether NETs appear in melanoma and affect melanoma cells. Indeed, human primary melanoma biopsies revealed neutrophils releasing NETs in all of 27 ulcerated melanomas, whereas NETs were absent in all of 7 non-ulcerated melanomas. However, the quantity of intratumoral NETs did not correlate with tumor progression of melanoma. Interestingly, in vitro assays showed that melanoma cells attach to NETs via integrin-mediated adhesion and that NETs inhibit tumor cell migration. Moreover, co-culturing of NETs and melanoma cells had a cytotoxic effect on melanoma cells resulting in necrosis. Hence, we discovered in vitro an antineoplastic role of NETs in melanoma.

Abstract 1049: Targeting YAP/TAZ pathway inhibits Ewing sarcoma metastasis

Abstract The term epithelial to mesenchymal transition (EMT) and its reverse (MET) describe the dynamic and reversible metamorphosis of cells from a highly organized to a loose migratory phenotype through cytoskeletal reorganization causing cellular plasticity. EMT/MET are inherent to normal embryonal development and wound healing, but cancer cells hijack the underlying mechanisms to enable oscillations between proliferation, invasion and migration that cause metastasis, the major killer of cancer patients. Recently, fluctuations of the oncoprotein EWS-FLI1 were identified to drive EMT/MET in Ewing sarcoma. We previously demonstrated that, in presence of EWS-FLI1, transcriptional co-activators MRTFB and TAZ are largely blocked from associating with TEAD and its target genes keeping tumor cells in a poorly migratory, highly proliferative state. In contrast, under EWS-FLI-low conditions, MRTFB and TAZ associate with YAP/TEAD complexes on chromatin resulting in cytoskeletal target gene activation and phenotypic transition to a highly migratory and low proliferative state. We therefore hypothesized that pharmacologic inhibition of YAP/TAZ/TEAD protein interaction should prevent Ewing sarcoma cells from EMT and consequently interfere with their metastatic potential. Verteporfin is a small molecule safely used in the treatment of age-related macular degeneration. Independent of its photosensitizing activity exploited in ophthalmology, it is a YAP/TAZ pathway -blocking compound. In vitro treatment of EWS-FLI1-low Ewing sarcoma cells with verteporfin resulted in decreased YAP/TAZ/TEAD complex formation in the nanomolar range, reversal of the de-repression of a EWS-FLI1 controlled EMT transcriptional signature, and inhibition of tumor cell migration in a Boyden chamber assay. Upon orthotopic implantation of TC71 Ewing sarcoma cells into the tibial crest of SCID beige mice, intra-peritoneal treatment of mice with 25mg verteporfin/kg/day before and after amputation of the affected limb led to a drastic decrease of lung metastases without affecting primary tumor growth and without obvious general toxicity. Therefore, YAP/TAZ pathway blockade holds promise as a potential metastasis-preventive strategy in the treatment of Ewing sarcoma patients with primary localized disease. Citation Format: Lisa Bierbaumer, Anna M. Katschnig, Branka Radic-Sarikas, Jeffrey R. Petro, Karin Mühlbacher, Dave N. Aryee, Anna R. Pötsch, Sandra Högler, Lukas Kenner, Aykut Uren, Heinrich Kovar. Targeting YAP/TAZ pathway inhibits Ewing sarcoma metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1049.

Activation of Slit2/Robo1 Signaling Promotes Tumor Metastasis in Colorectal Carcinoma through Activation of the TGF-β/Smads Pathway.

Slit2 (slit guidance ligand 2), a ligand of the Roundabout1 (Robo1) transmembrane receptor, is often overexpressed in colorectal carcinomas (CRCs). In this study, we performed data mining in the Metabolic gEne RApid Visualizer (MERAV) database and found that Slit2 and TGF-β1 (Transforming growth factor-β1) are highly expressed in carcinomas relative to those in tumor-free tissues from healthy volunteers or wild type mice. Furthermore, expression of Slit2 and TGF-β1 in CRCs increases with pathological stages. Serum levels of Slit2 in patients with CRC and in ApcMin/+ mice with spontaneous intestinal adenoma were significantly increased compared with those in healthy controls. Specific blockage of Slit2 binding to Robo1 inactivated TGF-β/Smads signaling and inhibited tumor cell migration and metastasis, which can be partially restored by treatment with TGF-β1. However, specific inhibition of TGF-β1/Smads signaling reduced CRC tumor cell migration and invasion without affecting cell proliferation. This study suggests that activation of Slit2/Robo1 signaling in CRC induces tumor metastasis partially through activation of the TGF-β/Smads pathway.

MicroRNA-124-3p suppresses cell migration and invasion by targeting ITGA3 signaling in bladder cancer

A growing body of studies have demonstrated the aberrant expression of microRNAs (miRNAs) contributes to human tumor metastasis. MicroRNA-124-3p (miR-124-3p), which is down-regulated in various cancers, has been found to be involved in several signaling pathways relevant to tumor cell migration and invasion. However, the roles of miR-124-3p in human bladder cancer remain unclear. This study aims to investigate the functional significance of miR-124-3p and to understand how it targets the integrin receptor, and thus affects the progression of human bladder cancer. Clinical specimens from 36 patients and three human bladder cancer cell lines were analyzed for miR-124-3p and integrin α3 (ITGA3) . To investigate the effects of miR-124-3p and ITGA3 on proliferation of bladder cancer cells, the MTT assay, colon-formation assay and flow cytometry were performed. In addition, wound healing assay and transwell assay were carried out to examine the migration and invasion of the bladder cancer cells transfected with miR-124-3p mimics or si-ITGA3. The luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were applied to validate the miR-124-3p directly binding with ITGA3. Finally, western blot was used to examine the expression level of the proteins involved in FAK/PI3K/AKT and FAK/Src signal pathway as well as epithelial-mesenchymal transition (EMT) process. The down-regulation of miR-124-3p and up-regulation of ITGA3 were observed in clinical specimens and bladder cancer cell lines. Overexpression of miR-124-3p or silencing ITGA3 inhibited tumor cell migration and invasion. Luciferase assay confirmed miR-124-3p directly targets ITGA3, and western blot suggested that miR-124-3p plays a crucial role in the EMT and metastasis of human bladder cancer through FAK/PI3K/AKT and FAK/Src signaling mechanism. Also, by targeting ITGA3, miR-124-3p can modulate the expression of N- and E-cadherin, and thus inhibit the EMT. By targeting ITGA3 and downstream FAK/PI3K/AKT and FAK/Src signaling pathways, miR-124-3p suppresses cell migration and invasion in bladder cancer. Our study reasonably speculates that miR-124-3p can be potentially developed as a therapeutic target and prognostic biomarker for bladder cancer.

SOX30 is a prognostic biomarker and chemotherapeutic indicator for advanced-stage ovarian cancer.

New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31-5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer. SOX30 coincidentally located at this chromosomal region has been determined as a new important tumor suppressor. However, the prognostic value, role and mechanism of SOX30 in ovarian cancer are unexplored. Here, we reveal that SOX30 is frequently overexpressed in ovarian cancer tissues and is associated with clinical stage and metastasis of ovarian cancer patients. High SOX30 expression predicts better OS and acts as an independent prognostic factor in advanced-stage patients, but is not associated with OS in early-stage patients. Based on the survival analyses, the advanced-stage patients with high SOX30 expression can receive platin- and/or taxol-based chemotherapy, whereas they should not receive chemotherapy containing gemcitabine or topotecan. Functionally, SOX30 strongly inhibits tumor cell migration and invasion in intro and suppresses tumor metastasis in vivo. SOX30 regulates some markers (E-CADHERIN, FIBRONECTIN, N-CADHERIN and VIMENTIN) and prevents the characteristics of epithelial-mesenchymal transition (EMT). SOX30 transcriptionally regulates the expression of E-CADHERIN, FIBRONECTIN and N-CADHERIN by binding to their promoters. Restoration of E-CADHERIN and/or N-CADHERIN when overexpressing SOX30 significantly reduces the anti-metastatic role of SOX30. Indeed, chemotherapy treatment containing platin or gemcitabine combined with SOX30 expression influences tumor cell metastasis and the survival of nude mice differently, which is closely associated with EMT. In conclusion, SOX30 antagonizes tumor metastasis by preventing EMT process that can be used to predict survival and incorporated into chemotherapeutics of advanced-stage ovarian cancer patients.

Low-dose zoledronate for the treatment of bone metastasis secondary to prostate cancer

BackgroundBisphosphonates (BPs) including zoledronate (zol) have become standard care for bone metastases as they effectively inhibit tumor-induced osteolysis and associated pain. Several studies have also suggested that zol has direct anti-tumor activity. Systemic administration at high doses is the current approach to deliver zol, yet it has been associated with debilitating side effects. Local therapeutic delivery offers the ability to administer much lower total dosage, while at the same time maintaining sustained high-local drug concentration directly at the target treatment site. Here, we aimed to assess effects of lower doses of zol on bone metastases over a longer time.MethodsProstate cancer cell line LAPC4 and prostate-induced bone metastasis cells were treated with zol at 1, 3 and 10 µM for 7 days. Following treatment, cell proliferation was assessed using Almarblue®, Vybrant MTT®, and Live/Dead® viability/cytotoxicity assays. Additionally, cell migration and invasion were carried out using Falcon™ cell culture inserts and Cultrex® 3D spheroid cell invasion assays respectively.ResultsWe show that treatment with 3–10 µM zol over 7-days significantly decreased cell proliferation in both the prostate cancer cell line LAPC4 and cells from spine metastases secondary to prostate cancer. Using the same low-dose and longer time course for treatment, we demonstrate that 10 µM zol also significantly inhibits tumor cell migration and 3D-cell growth/invasion.ConclusionsThis project harnesses the potential of using zol at low doses for longer treatment periods, which may be a viable treatment modality when coupled with biomaterials or biodevices for local delivery.

Ovatodiolide inhibits the oncogenicity and cancer stem cell-like phenotype of glioblastoma cells, as well as potentiate the anticancer effect of temozolomide

BackgroundOvatodiolide (Ova), a major bioactive diterpenoid isolate of Anisomeles indica has drawn considerable attention lately as an effective anticancer agent with several published works demonstrating its tumor-inhibitory activity in various cancer types. PurposeIn this study, we examined the modulatory effect of Ova on the oncogenicity, proliferation, and cancer stem cell-like traits of glioblastoma (GBM) cells, as well as investigated the underlying molecular mechanism for the anticancer activity of Ova in GBM cell lines, U-87MG and GBM8401. MethodsThe antiproliferative, apoptotic, and stemness-attenuating effects of Ova were evaluated using the sulforhodamine B (SRB) colorimetric assay, western blot and fluorescent immunocytochemistry. Cell apoptosis was analyzed based on variation in the expression levels of Bcl-2 family of regulator proteins Bax, Bak, Bcl-2 and Bcl-xL. ResultsOva induced the apoptosis of the U-87MG and GBM8401 cells, as well as effectively inhibited the proliferation and motility of the GBM cell lines in a dose- and time-dependent manner. Ova-induced apoptosis correlated with increased Bax/Bcl-2 ratio, while inhibition of tumor cell migration and colony formation was associated with reduced Slug, Vimentin, NCadherin and β-catenin protein expression and increased E-Cadherin. In addition, exposure to Ova inhibited tumorsphere formation, elicited downregulation of CD44, CD133, Sox2, and Oct4, as well as correlated with dysregulation of the JAK2-STAT3 signaling pathway. Furthermore, we showed for the first time to the best of our knowledge that Ova potentiate the chemotherapeutic effect of Temozolomide. ConclusionTaken together, our findings demonstrate the anticancer potential of Ova in GBM and its efficacy in the treatment of GBM as monotherapy and in combination with Temozolomide.

Antitumor activity in colorectal cancer induced by hinokiflavone.

Colorectal cancer is one of the most common malignant disease worldwide with highly metastatic potential. Identification of effective therapeutic treatment overcoming such disease is an urgent need. Our study focuses on hinokiflavone as an antitumor agent against colorectal cancer. MTT assay, cell colony formation assay, Hoechst staining, flow cytometry, Western blot analysis, real-time polymerase chain reaction, and migration and invasion assay were performed to identify the effects of hinokiflavone on cell proliferation, apoptosis, and metastasis. CT26 tumor-bearing mice model was conducted to explore the antitumor activity of hinokiflavone in vivo. Immunohistochemistry staining was used to detect the protein expression of Ki-67, cleaved caspase-3, and MMP9 in treated tumors. Acute toxicity was evaluated by serological and hematological analyses, and drug side effect on organs was evaluated by hematoxylin and eosin staining. Hinokiflavone reduced the proliferation, migration, and invasion and promoted the apoptosis in colorectal tumor cells in vitro. Treatment of hinokiflavone at a tolerable and safe dose (50mg/kg) significantly suppressed tumor growth in mice bearing CT26 tumors by reducing tumor proliferation and metastasis and inducing apoptosis. Mechanically, treatment of hinokiflavone induced apoptosis by loss of mitochondrial transmembrane potential and increased reactive oxygen species generation. Hinokiflavone suppressed colorectal tumor cell proliferation, induced apoptosis via the reactive oxygen species-mitochondria-mediated apoptotic pathway, and inhibited tumor cell migration and invasion. Antitumor activity of hinokiflavone was also validated in mice model without observed toxicity. Our findings suggested that the plant-derived hinokiflavone could be used as an antitumor agent against colorectal cancer.

Long non-coding RNA CASC2 upregulates PTEN to suppress pancreatic carcinoma cell metastasis by downregulating miR-21

BackgroundThe mechanism of pancreatic cancer metastasis remains poorly understood. Recently, lncRNA CASC2 has been demonstrated to be a tumor suppressor in various types of cancer. This study aimed to explore the mechanism of CASC2 in the regulation of pancreatic cancer metastasis.MethodsThe expression levels of CASC2 and miR-21 in pancreatic cells were detected by qRT-PCR. Using specific expression vectors, including mimics or shRNA, the expression levels of CASC2, miR-21 and PTEN in pancreatic cells were altered. The association between CASC2, miR-21 and PTEN was detected. Then, cell migration and invasion were assessed using the transwell assay.ResultsCASC2 expression was downregulated in the pancreatic cancer cell lines CAPAN-1, BxPC-3, JF305, PANC-1 and SW1990 compared with levels in normal human pancreatic HPDE6-C7 cells. CACS2 overexpression inhibited the migration and invasion of PANC-1 cells and significantly inhibited the expression of miR-21 and PTEN. MiR-21 was a direct target of CACS2. The overexpression of miR-21 significantly abolished the antimetastatic effects of CASC2 on PANC-1 cells. Moreover, the downregulation of PTEN significantly abolished the antimetastatic effects of CASC2.ConclusionCASC2 functions as a tumor suppressor in pancreatic cancer cells to inhibit tumor cell migration and invasion. Our work revealed a novel regulatory mechanism of the CASC2/miR-21/PTEN axis that may be important in pancreatic cancer.

Activation of the AKT/FOXO3a Signaling Pathway during Breast Cancer Inhibition In Vivo and In Vitro by Amauroderma rude (Agaricomycetes).

We previously reported that Amauroderma rude polysaccharides (AR) displayed strong immunomodulatory tumor-suppressive effects in mice. The current study was designed to explore the potential mechanism by which AR polysaccharides inhibit tumor growth. We found that AR could effectively induce cell death in 4T1 and MDA-MB-231 breast cancer cells. AR could also inhibit tumor cell migration and invasion, significantly promote apoptosis in 4T1 cells, and significantly increase CDK4, CDK6, cylinD1, and P27 mRNA expression in mice. Additionally, AR was able to significantly increase FOXO3a expression and decrease p-AKT expression both in vitro and in vivo, indicating that the AKT/FOXO3a signaling pathway had been activated during the inhibitory process.

Knockdown of LncRNA RHPN1-AS1 Inhibits Cell Migration, Invasion and Proliferation in Head and Neck Squamous Cell Carcinoma.

Previous studies have revealed that long non-coding RNAs (lncRNAs) are involved in head and neck squamous cell carcinoma (HNSCC) progression. However, the detailed roles of lncRNA RHPN1-AS1 remain to be elucidated. In this study, by analyzing online RNA-Seq data, we found that RHPN1-AS1 was upregulated in HNSCC tissues and that its expression level was associated with neoplasm histologic grade. High expression of RHPN1-AS1 was also confirmed in HNSCC tissues. Knockdown of RHPN1-AS1 inhibited tumor cell migration, invasion and proliferation in HNSCC. Furthermore, inhibition of RHPN1-AS1 suppressed the expression of epithelial-mesenchymal transition (EMT)-related genes (β-Catenin, Claudin-1 and Vimentin) in HNSCC cells. Collectively, our results suggest that RHPN1-AS1, acting as an oncogene, may be a potential diagnostic and therapeutic target in HNSCC.

The Wnt modulator ICG‑001 mediates the inhibition of nasopharyngeal carcinoma cell migration in vitro via the miR‑150/CD44 axis.

The Wnt signaling pathway is known to serve an important role in the control of cell migration. The present study analyzed the mechanisms underlying the invitro modulation of the migration of nasopharyngeal carcinoma (NPC) cells by the CREB‑binding protein/catenin antagonist and Wnt modulator ICG‑001. The results revealed that ICG‑001‑mediated inhibition of tumor cell migration involved downregulated mRNA and protein expression of the Wnt target gene cluster of differentiation (CD)44. It was also demonstrated that ICG‑001 downregulated the expression of CD44, and this effect was accompanied by restored expression of microRNA (miRNA)‑150 in various NPC cell lines. Using a CD44 3'‑untranslated region luciferase reporter assay, miR‑150 was confirmed to be a novel CD44‑targeting miRNA, which could directly target CD44 and subsequently regulate the migration of NPC cells. The present study provides further insight into the inhibition of tumor cell migration through the modulation of miRNA expression by the Wnt modulator ICG‑001.

Experimental Evidence of the Antitumor, Antimetastatic and Antiangiogenic Activity of Ellagic Acid.

Ellagic acid (EA) is a naturally occurring polyphenolic compound endowed with strong antioxidant and anticancer properties that is present in high quantity in a variety of berries, pomegranates, and dried fruits. The antitumor activity of EA has been mostly attributed to direct antiproliferative and apoptotic effects. Moreover, EA can inhibit tumour cell migration, extra-cellular matrix invasion and angiogenesis, all processes that are crucial for tumour infiltrative behaviour and the metastatic process. In addition, EA may increase tumour sensitivity to chemotherapy and radiotherapy. The aim of this review is to summarize the in vitro and in vivo experimental evidence supporting the anticancer activity of pure EA, its metabolites, and EA-containing fruit juice or extracts in a variety of solid tumour models. The EA oral administration as supportive therapy to standard chemotherapy has been recently evaluated in small clinical studies with colorectal or prostate cancer patients. Novel formulations with improved solubility and bioavailability are expected to fully develop the therapeutic potential of EA derivatives in the near future.